9-127944857-T-C

Variant names:

• chr9-127944857-T-C
• NM_001035254.3:c.959A>G

Variant summary

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

The NM_001035254.3(EEIG1):​c.959A>G​(p.Asp320Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: EEIG1 NM_001035254.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.24

Genes affected

EEIG1 (HGNC:31419): (estrogen-induced osteoclastogenesis regulator 1)

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 rank	MANE	Protein	UniProt
EEIG1	NM_001035254.3	c.959A>G	p.Asp320Gly	missense_variant	Exon 9 of 11	ENST00000373095.6	NP_001030331.1
EEIG1	NM_203305.3	c.533A>G	p.Asp178Gly	missense_variant	Exon 6 of 8		NP_976050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEIG1	ENST00000373095.6	c.959A>G	p.Asp320Gly	missense_variant	Exon 9 of 11	5	NM_001035254.3	ENSP00000362187.1
EEIG1	ENST00000373084.8	c.533A>G	p.Asp178Gly	missense_variant	Exon 6 of 8	1		ENSP00000362176.4
EEIG1	ENST00000300434.3	n.643A>G		non_coding_transcript_exon_variant	Exon 4 of 6	1
EEIG1	ENST00000465821.5	n.432A>G		non_coding_transcript_exon_variant	Exon 4 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460276 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 726536

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.959A>G (p.D320G) alteration is located in exon 9 (coding exon 9) of the FAM102A gene. This alteration results from a A to G substitution at nucleotide position 959, causing the aspartic acid (D) at amino acid position 320 to be replaced by a glycine (G). 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	0.27
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.18
Sift	Benign	0.076	T;T
Sift4G	Benign	0.13	T;D
Polyphen		0.58	P;.
Vest4		0.54
MutPred		0.45		Loss of disorder (P = 0.0769);.;
MVP		0.63
MPC		0.92
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.32
gMVP		0.57

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: chr9-130707136;