chr10-102471284-A-T

Position:

• chr10-102471284-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024789.4(MFSD13A):​c.716A>T​(p.Glu239Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MFSD13A NM_024789.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.32

Genes affected

MFSD13A (HGNC:26196): (major facilitator superfamily domain containing 13A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC124902493 (HGNC:):

ACTR1A (HGNC:167): (actin related protein 1A) This gene encodes a 42.6 kD subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit is present in 8-13 copies per dynactin molecule, and is the most abundant molecule in the dynactin complex. It is an actin-related protein, and is approximately 60% identical at the amino acid level to conventional actin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22305027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD13A	NM_024789.4	c.716A>T	p.Glu239Val	missense_variant	6/10	ENST00000238936.8	NP_079065.2
LOC124902493	XR_007062270.1	n.81+1551T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD13A	ENST00000238936.8	c.716A>T	p.Glu239Val	missense_variant	6/10	5	NM_024789.4	ENSP00000238936	P1
MFSD13A	ENST00000369931.3	c.263A>T	p.Glu88Val	missense_variant	5/6	1		ENSP00000358947
MFSD13A	ENST00000469294.1	n.104A>T		non_coding_transcript_exon_variant	2/3	3
ACTR1A	ENST00000636707.1	c.*138+1551T>A		intron_variant, NMD_transcript_variant		5		ENSP00000490634

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 33

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

Oct 29, 2021

The c.716A>T (p.E239V) alteration is located in exon 6 (coding exon 4) of the MFSD13A gene. This alteration results from a A to T substitution at nucleotide position 716, causing the glutamic acid (E) at amino acid position 239 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T;.
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.11
Sift	Benign	0.14	T;D
Sift4G	Benign	0.23	T;D
Polyphen		0.0010	B;D
Vest4		0.41
MutPred		0.51		Loss of disorder (P = 0.0311);.;
MVP		0.47
MPC		0.38
ClinPred		0.84	D
GERP RS		5.6
Varity_R		0.14
gMVP		0.48

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-104231041;