4-94232198-T-C

Variant names:

• chr4-94232198-T-C
• rs3106136
• NM_020159.5:c.369-1756T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020159.5(SMARCAD1):​c.369-1756T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 150,778 control chromosomes in the GnomAD database, including 12,714 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12714 hom., cov: 32)
• Consequence: SMARCAD1 NM_020159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 8 publications found

Genes affected

SMARCAD1 (HGNC:18398): (SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD/H box 1) This gene encodes a member of the SNF subfamily of helicase proteins. The encoded protein plays a critical role in the restoration of heterochromatin organization and propagation of epigenetic patterns following DNA replication by mediating histone H3/H4 deacetylation. Mutations in this gene are associated with adermatoglyphia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

SMARCAD1 Gene-Disease associations (from GenCC):

• ectodermal dysplasia syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
• isolated congenital adermatoglyphia

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• palmoplantar keratoderma-sclerodactyly syndrome

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P
• absence of fingerprints-congenital milia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020159.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAD1	NM_020159.5	MANE Select	c.369-1756T>C		intron	N/A	NP_064544.2	Q9H4L7-1
	SMARCAD1	NM_001128429.3		c.369-1756T>C		intron	N/A	NP_001121901.1	Q9H4L7-2
	SMARCAD1	NM_001128430.2		c.369-1756T>C		intron	N/A	NP_001121902.1	Q9H4L7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCAD1	ENST00000354268.9	TSL:1 MANE Select	c.369-1756T>C		intron	N/A	ENSP00000346217.4	Q9H4L7-1
	SMARCAD1	ENST00000359052.8	TSL:1	c.369-1756T>C		intron	N/A	ENSP00000351947.4	Q9H4L7-2
	SMARCAD1	ENST00000457823.6	TSL:1	c.369-1756T>C		intron	N/A	ENSP00000415576.2	Q9H4L7-2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60437 AN: 150664 Hom.: 12691 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.386

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.401 AC: 60477 AN: 150778 Hom.: 12714 Cov.: 32 AF XY: 0.408 AC XY: 30065 AN XY: 73718

African (AFR) AF: 0.313 AC: 12621 AN: 40280

American (AMR) AF: 0.491 AC: 7488 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1328 AN: 3472

East Asian (EAS) AF: 0.715 AC: 3694 AN: 5164

South Asian (SAS) AF: 0.587 AC: 2827 AN: 4812

European-Finnish (FIN) AF: 0.386 AC: 4068 AN: 10550

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27140 AN: 67960

Other (OTH) AF: 0.393 AC: 825 AN: 2098

Alfa AF: 0.347 Hom.: 3649

Bravo AF: 0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.7
DANN	Benign	0.34
PhyloP100		2.0
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: rs3106136; hg19: chr4-95153349;