NM_015123.3:c.1186A>T

Variant names:

• chr3-69196303-T-A
• rs9310141
• NM_015123.3:c.1186A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015123.3(FRMD4B):​c.1186A>T​(p.Thr396Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T396M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRMD4B NM_015123.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 28 publications found

Genes affected

FRMD4B (HGNC:24886): (FERM domain containing 4B) This gene encodes a GRP1-binding protein which contains a FERM protein interaction domain as well as two coiled coil domains. This protein may play a role as a scaffolding protein. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03560558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD4B	NM_015123.3	c.1186A>T	p.Thr396Ser	missense_variant	Exon 14 of 23	ENST00000398540.8	NP_055938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD4B	ENST00000398540.8	c.1186A>T	p.Thr396Ser	missense_variant	Exon 14 of 23	1	NM_015123.3	ENSP00000381549.3
FRMD4B	ENST00000478263.5	c.142A>T	p.Thr48Ser	missense_variant	Exon 4 of 13	1		ENSP00000418682.1
FRMD4B	ENST00000462512.1	c.319A>T	p.Thr107Ser	missense_variant	Exon 4 of 5	4		ENSP00000419869.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457560 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725208

African (AFR) AF: 0.00 AC: 0 AN: 33350

American (AMR) AF: 0.00 AC: 0 AN: 43876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.00 AC: 0 AN: 85620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109748

Other (OTH) AF: 0.00 AC: 0 AN: 60176

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.42
DEOGEN2	Benign	0.0017	T;T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.10	T;T;T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.036	T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	-1.5	N;.;.
PhyloP100		1.7
PrimateAI	Benign	0.40	T
PROVEAN	Benign	1.7	N;N;N
REVEL	Benign	0.20
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.025
MutPred		0.19		Loss of sheet (P = 0.0315);.;.;
MVP		0.40
MPC		0.046
ClinPred		0.62	D
GERP RS		6.1
Varity_R		0.040
gMVP		0.081
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9310141; hg19: chr3-69245454;