9-127944655-C-T

Variant names:

• chr9-127944655-C-T
• rs1461397159
• NM_001035254.3:c.1069G>A

Variant summary

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

The NM_001035254.3(EEIG1):​c.1069G>A​(p.Asp357Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,284 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: EEIG1 NM_001035254.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20

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.1069G>A	p.Asp357Asn	missense_variant	Exon 10 of 11	ENST00000373095.6	NP_001030331.1
EEIG1	NM_203305.3	c.643G>A	p.Asp215Asn	missense_variant	Exon 7 of 8		NP_976050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EEIG1	ENST00000373095.6	c.1069G>A	p.Asp357Asn	missense_variant	Exon 10 of 11	5	NM_001035254.3	ENSP00000362187.1
EEIG1	ENST00000373084.8	c.643G>A	p.Asp215Asn	missense_variant	Exon 7 of 8	1		ENSP00000362176.4
EEIG1	ENST00000300434.3	n.753G>A		non_coding_transcript_exon_variant	Exon 5 of 6	1
EEIG1	ENST00000465821.5	n.542G>A		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460284 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 726490

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: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1069G>A (p.D357N) alteration is located in exon 10 (coding exon 10) of the FAM102A gene. This alteration results from a G to A substitution at nucleotide position 1069, causing the aspartic acid (D) at amino acid position 357 to be replaced by an asparagine (N). 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	0.29
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.0	N;D
REVEL	Benign	0.21
Sift	Benign	0.16	T;T
Sift4G	Benign	0.10	T;T
Polyphen		1.0	D;.
Vest4		0.75
MutPred		0.38		Gain of MoRF binding (P = 0.0453);.;
MVP		0.49
MPC		1.2
ClinPred		0.90	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.75

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: rs1461397159; hg19: chr9-130706934; COSMIC: COSV100305529; COSMIC: COSV100305529;