chr15-74906740-T-C

Position:

• chr15-74906740-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020447.5(FAM219B):​c.61A>G​(p.Ser21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000084 in 1,190,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: FAM219B NM_020447.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0200

Genes affected

FAM219B (HGNC:24695): (family with sequence similarity 219 member B)

FAM219B (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0317612).
• BP6: Variant 15-74906740-T-C is Benign according to our data. Variant chr15-74906740-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3092308.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM219B	NM_020447.5	c.61A>G	p.Ser21Gly	missense_variant	1/5	ENST00000357635.10	NP_065180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM219B	ENST00000357635.10	c.61A>G	p.Ser21Gly	missense_variant	1/5	1	NM_020447.5	ENSP00000350260.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.40e-7 AC: 1 AN: 1190684 Hom.: 0 Cov.: 30 AF XY: 0.00000175 AC XY: 1 AN XY: 572622

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000360

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.1
DANN	Benign	0.46
DEOGEN2	Benign	0.0026	T;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.51	.;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.032	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.13	N;N;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.32	N;N;N
REVEL	Benign	0.012
Sift	Benign	0.86	T;T;T
Sift4G	Benign	0.60	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.071
MutPred		0.12		Loss of phosphorylation at S21 (P = 0.001);Loss of phosphorylation at S21 (P = 0.001);Loss of phosphorylation at S21 (P = 0.001);
MVP		0.030
MPC		0.25
ClinPred		0.048	T
GERP RS		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.034
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs1331531485; hg19: chr15-75199081;