11-65399750-A-C

Position:

• chr11-65399750-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031904.5(FRMD8):​c.818A>C​(p.His273Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FRMD8 NM_031904.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.533

Genes affected

FRMD8 (HGNC:25462): (FERM domain containing 8) Involved in positive regulation of tumor necrosis factor production. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FRMD8 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD8	NM_031904.5	c.818A>C	p.His273Pro	missense_variant	8/11	ENST00000317568.10	NP_114110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD8	ENST00000317568.10	c.818A>C	p.His273Pro	missense_variant	8/11	1	NM_031904.5	ENSP00000319726.4
FRMD8	ENST00000416776.6	c.716A>C	p.His239Pro	missense_variant	7/10	2		ENSP00000392111.2
FRMD8	ENST00000355991.9	c.650A>C	p.His217Pro	missense_variant	7/10	2		ENSP00000348270.5
FRMD8	ENST00000531151.1	n.401A>C		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.818A>C (p.H273P) alteration is located in exon 8 (coding exon 7) of the FRMD8 gene. This alteration results from a A to C substitution at nucleotide position 818, causing the histidine (H) at amino acid position 273 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.39	T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.064
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.38	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.43
Sift	Benign	0.045	D;T;D
Sift4G	Benign	0.20	T;T;T
Polyphen		0.88	P;B;.
Vest4		0.49
MutPred		0.49		Gain of ubiquitination at K278 (P = 0.0797);.;.;
MVP		0.76
MPC		0.48
ClinPred		0.34	T
GERP RS		3.4
Varity_R		0.55
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65167221;