16-30704198-C-G

Variant names:

• chr16-30704198-C-G
• rs79656879
• NM_006662.3:c.189C>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006662.3(SRCAP):​c.189C>G​(p.Pro63Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,614,168 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P63P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.023 (98 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (102 hom.)
• Consequence: SRCAP NM_006662.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.261
• Publications: 2 publications found

Genes affected

SRCAP (HGNC:16974): (Snf2 related CREBBP activator protein) This gene encodes the core catalytic component of the multiprotein chromatin-remodeling SRCAP complex. The encoded protein is an ATPase that is necessary for the incorporation of the histone variant H2A.Z into nucleosomes. It can function as a transcriptional activator in Notch-mediated, CREB-mediated and steroid receptor-mediated transcription. Mutations in this gene cause Floating-Harbor syndrome, a rare disorder characterized by short stature, language deficits and dysmorphic facial features. [provided by RefSeq, Feb 2012]

SRCAP Gene-Disease associations (from GenCC):

• developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Floating-Harbor syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000282034 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 16-30704198-C-G is Benign according to our data. Variant chr16-30704198-C-G is described in ClinVar as Benign. ClinVar VariationId is 160033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.261 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRCAP	NM_006662.3	MANE Select	c.189C>G	p.Pro63Pro	synonymous	Exon 4 of 34	NP_006653.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRCAP	ENST00000262518.9	TSL:2 MANE Select	c.189C>G	p.Pro63Pro	synonymous	Exon 4 of 34	ENSP00000262518.4
	ENSG00000282034	ENST00000380361.7	TSL:2	n.132C>G		non_coding_transcript_exon	Exon 1 of 31	ENSP00000369719.3
	SRCAP	ENST00000411466.7	TSL:3	c.189C>G	p.Pro63Pro	synonymous	Exon 4 of 34	ENSP00000405186.3

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3465 AN: 152160 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00237

Gnomad OTH AF: 0.0186

GnomAD2 exomes AF: 0.00795 AC: 1984 AN: 249552 AF XY: 0.00662

Gnomad AFR exome AF: 0.0730

Gnomad AMR exome AF: 0.00460

Gnomad ASJ exome AF: 0.0354

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000557

Gnomad NFE exome AF: 0.00238

Gnomad OTH exome AF: 0.00627

GnomAD4 exome AF: 0.00406 AC: 5939 AN: 1461890 Hom.: 102 Cov.: 31 AF XY: 0.00379 AC XY: 2759 AN XY: 727246

African (AFR) AF: 0.0734 AC: 2458 AN: 33480

American (AMR) AF: 0.00525 AC: 235 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0345 AC: 901 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000603 AC: 52 AN: 86256

European-Finnish (FIN) AF: 0.000824 AC: 44 AN: 53420

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.00155 AC: 1724 AN: 1112010

Other (OTH) AF: 0.00811 AC: 490 AN: 60396

GnomAD4 genome AF: 0.0228 AC: 3473 AN: 152278 Hom.: 98 Cov.: 32 AF XY: 0.0219 AC XY: 1631 AN XY: 74452

African (AFR) AF: 0.0710 AC: 2950 AN: 41556

American (AMR) AF: 0.0125 AC: 191 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00237 AC: 161 AN: 68028

Other (OTH) AF: 0.0184 AC: 39 AN: 2114

Alfa AF: 0.00628 Hom.: 2

Bravo AF: 0.0259

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00229

EpiControl AF: 0.00296

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.3
DANN	Benign	0.73
PhyloP100		-0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs79656879; hg19: chr16-30715519;