20-6119441-A-T

Variant names:

• chr20-6119441-A-T
• NM_017671.5:c.114T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_017671.5(FERMT1):​c.114T>A​(p.His38Gln) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FERMT1 NM_017671.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

Genes affected

FERMT1 (HGNC:15889): (FERM domain containing kindlin 1) This gene encodes a member of the fermitin family, and contains a FERM domain and a pleckstrin homology domain. The encoded protein is involved in integrin signaling and linkage of the actin cytoskeleton to the extracellular matrix. Mutations in this gene have been linked to Kindler syndrome. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.941

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT1	NM_017671.5	c.114T>A	p.His38Gln	missense_variant	Exon 2 of 15	ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2	c.114T>A	p.His38Gln	missense_variant	Exon 2 of 15		XP_024307703.1
FERMT1	XM_047440259.1	c.114T>A	p.His38Gln	missense_variant	Exon 2 of 15		XP_047296215.1
FERMT1	XM_047440260.1	c.-155T>A		5_prime_UTR_variant	Exon 1 of 14		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000217289.9	c.114T>A	p.His38Gln	missense_variant	Exon 2 of 15	1	NM_017671.5	ENSP00000217289.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.71	D;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;.
Polyphen		1.0	D;.
Vest4		0.89
MutPred		0.76		Loss of catalytic residue at L37 (P = 0.218);Loss of catalytic residue at L37 (P = 0.218);
MVP		0.66
MPC		0.85
ClinPred		0.99	D
GERP RS		-1.6
Varity_R		0.72
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-6100088;